Airway hyperresponsiveness in asthma: not just a matter of airway inflammation
- aCattedra di Fisiopatologia Respiratoria, Dipartimento di Scienze Motorie e Riabilitative, Università di Genova, Genova, Italy, bServizio di Fisiopatologia Respiratoria, Ospedale S. Croce e Carle, Cuneo, Italy
- Professor V Brusasco, Dipartimento di Scienze Motorie e Riabilitative Facoltà di Medicina e Chirurgia, Università di Genova, Largo R Benzi 10, 16132 Genova, Italy.
According to the most recent definition, bronchial asthma is a chronic inflammatory disorder of the airways associated with reversible airway obstruction and increased airway responsiveness to a variety of stimuli.1 An intuitive inference from this definition is that a causal relationship may exist between airway inflammation and airway hyperresponsiveness. Along this line of reasoning, most of the research in the last two decades in this field was aimed at identifying inflammatory cell products possibly responsible for the pathogenesis of bronchial asthma and airway hyperresponsiveness.2 However, the common observation that the asthmatic airways are equally hyperresponsive to a variety of different stimuli does challenge the idea that a single inflammatory cell or mediator may be central to the pathogenesis of asthma and airway hyperresponsiveness and focuses on the importance of an altered mechanical response of the target organ. This view has been recently corroborated by the finding that airway responsiveness of normal individuals may become similar to that of asthmatics by simply changing the pattern of breathing during the bronchial challenge.3It is therefore legitimate to wonder how much of airway hyperresponsiveness is due to inflammation or to inherent predisposing factors.
The aims of the present review are to show that airway narrowing in asthma is the ultimate result of an interaction between complex and multiple mechanisms not necessarily and uniquely related to airway inflammation, and to revisit the evidence on which the theorem “airway inflammation equal to airway hyperresponsiveness” has been constructed.
Mechanisms of airway narrowing in asthma
Airway calibre in vivo is the result of a delicate balance between the force generated by the airway smooth muscle (ASM) and a number of opposing factors.4 The latter are mainly represented by autonomic mechanisms that tend to limit the ASM tone and by mechanical forces that oppose ASM shortening.
AIRWAY SMOOTH MUSCLE (ASM)
Although it is widely …